PhD Scientific Days 2022

Pathology and Oncology I. (Poster discussion will take place in the Aula during the Coffee Break)

Proteomic Profiling of Primary Tumors and Corresponding Brain Metastases of Surgically Treated Lung Adenocarcinoma Patients Reveal Increased Inter-tumoral Heterogeneity

Text of the abstract

Introduction: Brain metastasis (BM), the most common distant metastasis in lung adenocarcinoma (LADC), has a significant negative impact on patients’ outcomes. Therefore, novel treatment and follow-up strategies are urgently needed in these patients.

Aims: Our aim was to investigate the inter-tumoral heterogeneity in brain metastatic LADC patients with proteomic approaches, as well as to assess the impact of the existing proteomic pattern on the timing of BMs.

Method: Proteomic profiling was conducted on 20 surgically resected primary- and brain metastatic LADC samples via label-free shotgun proteomics. Large-scale protein identification and quantitation were followed by in-depth bioinformatical and statistical analyses. Proteomic data were correlated with clinicopathological parameters and the timing of BMs.

Results: Out of the 6,821 proteins quantified and identified in the tumor samples, 1,496 proteins were differentially expressed between primary LADCs and corresponding BMs. 1D annotation enrichment analysis revealed that pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- vs. slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and BMs, respectively. Specifically, we found that metabolic pathways and the ribosome pathway were upregulated in the fast-progressing patients (vs. slow-progressing individuals), whereas, cell-cell interaction- and immune system-related pathways were downregulated in these patients and in those with multiple BMs.

Conclusion: By shedding light on the specific proteomic profiles of primary and brain metastatic LADCs, our results might provide insights into the biological processes involved in the metastatic spread, and moreover, might contribute to the development of personalized follow-up strategies in the clinics.

Funding: Zs.M. was supported by the UNKP‐ 20‐ 3 and UNKP-21-3 New National Excellence Program of the Ministry for Innovation and Technology of Hungary.

E-mail: megyesfalvi.zsolt@semmelweis-univ.hu
University and Doctoral School: Semmelweis University – Károly Rácz Doctoral School of Clinical Medicine
Supervisor: Dr. Balázs Döme